The shedding of cells into the circulation is an intrinsic property of the malignant tumor, and this feature provides important information with regard to the diagnosis, staging, treatment response and survival of cancer patients. For example, Pantel et al found the number of circulating tumor cells (CTCs) in the blood is correlated with the aggressiveness of the cancer as well as the efficacy of the therapy. (Pantel, K. et. al., “Detection, clinical relevance and specific biological properties of disseminating tumor cells”, Nat Rev Cancer, 2008, 8(5):329-40).
However, CTCs, as few as one per 109 blood cells in patients with metastatic cancer, are rare cells. This makes the detection and isolation of CTCs technically challenging (see Kahnet al. Breast Cancer Res Treat 2004, 86:237-47). An enrichment process is therefore necessary to effectively detect and isolate CTCs.
An example of such enrichment process is the use of a highly overexpressed cell surface biomarker with high specificity and sensitivity for CTCs, such as the epithelial cell adhesion molecule (EpCAM). The Cellsearch System™ (Veridex), the only FDA-approved platform for CTC detection, utilizes anti-EpCAM antibody-coated magnetic nanoparticles to capture and enrich CTCs, followed by cytokeratin immunostaining. The AdnaTest (AdnaGen AG, Germany), another commercially available system for CTC detection, adopts similar immunomagnetic approach by using anti-EpCAM and Mucin 1 (MUC1) conjugated magnetic beads. More recently, “CTC chips” based on anti-EpCAM antibody-coated microfluidics chip were developed for CTC detection and enrichment (Nagrath et al, Nature 2007, 450:1235-9). However, the disadvantage of the above techniques is the low detection rate of pure CTCs, due to the non-specific binding of blood cells with anti-EpCAM antibody.
In order to maximize the detection and isolation of CTCs, it is necessary to reduce the nonspecific binding of other circulating blood cells. This can be achieved by surface modification with bioinert materials. For example, Kaladhar et al. observed a significant fewer circulating blood cells (e.g. platelets, leukocytes, and erythrocytes) binding onto the solid substrate modified with supported monolayer of various lipid compositions containing phosphatidyl-choline, cholesterol, and glycolipid (Kaladhar et al, Langmuir 2004, 20; 11115-22 and Kaladhar et al, J Biomed Mater Res A 2006, 79A:23-35).
Despite the advance in the detection and isolation CTCs technology, there is still a need for a more specific and effective method for detecting, purification and releasing CTCs and other biological substances for further cultivation and characterization.